Efficacy and Safety of a Dispersible Tablet of GPO-Deferasirox Monotherapy among Children with Transfusion-Dependent Thalassemia and Iron Overload.

The study aimed to determine efficacy and safety of generic deferasirox monotherapy. Deferasirox was administered in transfusion-induced iron overloaded thalassemia. Efficacy was defined as responders and nonresponders by ≤ 15 reduced serum ferritin from baseline. Adverse events were also monitored. Fifty-two patients with mainly Hb E/ß-thalassemia at the mean (SD) age of 8.7 (4.1) years, were enrolled. The mean (SD) daily transfusion iron load was 0.47 (0.1) mg/kg and maximum daily deferasirox was 35.0 (6.2) mg/kg. Altogether, 52, 40 and 18 patients completed the first, second and third years of study, respectively. The median baseline serum ferritin 2,383 ng/mL decreased to 1,478, 1,038 and 1,268 ng/mL at the end of first, second and third years, respectively, with overall response rate at 73.1% (38/52). Patients with baseline serum ferritin >2,500 ng/mL showed a change in serum ferritin higher than those ≤2,500 ng/mL starting from the 9th month of chelation. Adverse events were found in 5 of 52 patients (9.6%) including transaminitis (n = 2), one each of proteinuria, rash and proximal tubular dysfunction which resolved after transient stopping or decreasing the chelation dose. Generic deferasirox was effective and safe among pediatric patients with transfusion-induced iron overloaded thalassemia.

Effect of Food on the Pediatric Dispersible Tablet Formulations of TRIUMEQ and DOVATO in Healthy Adult Participants.

This randomized food effect study in healthy adult participants examined dispersible tablet formulations of fixed-dose combinations of dolutegravir/abacavir/lamivudine (TRIUMEQ) and dolutegravir/lamivudine (DOVATO). While adult tablet formulations of these combinations are currently approved for the treatment of human immunodeficiency virus, alternate formulations for children are urgently needed to facilitate appropriate pediatric dosing for patients who may have difficulty swallowing a conventional tablet. This study compared the effect of a high-fat, high-calorie meal on the pharmacokinetics, safety, and tolerability of dispersible tablet (DT) formulations of the two-drug and three-drug regimens, with administration under fasting conditions. Both the two-drug and three-drug dispersible tablet formulations, administered under fasting conditions and following a high-fat, high-calorie meal, were well tolerated in healthy participants. There were no clinically relevant differences in drug exposure for either regimen when administered with a high-fat meal as compared to under fasting conditions. Safety observations were similar for both treatments, either in the fed or fasted state. Both TRIUMEQ DT and DOVATO DT formulations can be administer with or without food.

Evaluation of the Effect of Ethyl Acrylate-Methyl Methacrylate Copolymer in Racecadotril Dispersible Tablet.

Objectives: Racecadotril is an anti-diarrheal drug that has the indication to reduce the secretion of water and electrolytes into the intestine. It has an unpleasant taste, when administered orally. The presenting study developed a pharmaceutical racecadotril dispersible tablet, which masked the unpleasent taste using wet granulation method. For this reason, the effect of the number of ethylacrylate-methylmethacrylate copolymers (Eudragit® NE 30D) in taste masking and in vitro dissolution of the finished product was investigated. Materials and Methods: Taste-masked racecadotril granules were prepared using Eudragit® NE 30D and the ratio between the amounts of racecadotril and Eudragit® NE 30D involved in the formulation was optimized. The products obtained in the dispersible tablet dosage form were evaluated in terms of taste and in vitro dissolution studies. In vitro dissolution profiles of the products obtained in this study were compared with reference product Tiorfan® granules for oral suspension manufactured by Bioprojet Pharma (Paris, France). A method of apparatus II (paddle), 900 mL, pH 4.5 acetate buffer + 1% sodium dodecyl sulfate (SDS) and 100 rpm at 37.0 ± 0.5°C was adopted. Results: Results of the studies have shown that the formulation should have Eudragit® NE 30D higher than 1% by weight of racecadotril to satisfy the taste-masking ability and the formulation should have Eudragit® NE 30D equal or lower than 10% by weight of racecadotril to have better release characteristic to be compatible with reference product. Conclusion: Our results demonstrated that a chemically long-term stable racecadotril dispersible tablet product, whose taste is efficiently masked using wet granulation method with an acceptable release profile was obtained with Eudragit® NE 30D ratio higher than 1% and equal or lower than 10% by weight of racecadotril. The developed formulation can increase patient compliance.

A new dual function orodissolvable/dispersible meclizine HCL tablet to challenge patient inconvenience: in vitro evaluation and in vivo assessment in human volunteers.

Meclizine hydrochloride (MCZ), a first-generation antihistamine of the piperazine class, is antiemetic and intended for the management of nausea and vomiting with few adverse effects. The introduction of orodispersible tablet (ODT) would solve the problems encountered in the administration of this drug to pediatric, geriatric, and psychiatric patients. It would be even more advantageous if the MCZ tablet could provoke rapid and prolonged efficacy. Achieving concomitant rapid and prolonged drug therapeutic effects in orodissolvable/dispersible dosage forms would be challenging. In this respect, the authors prepared tablets with coats and cores for immediate and prolonged drug absorption. To achieve this goal, nanoparticles of MCZ from chitosan (CS) and shellac (SH) were prepared by ionic crosslinking and then directly compressed with excipients to form the core in a coated tablet. The immediate release coat with MCZ with the same excipients as in the core was amenable by direct compression. MCZ in the coat dissolved in the presence of a superdisintegrant, leading to rapid absorption from the buccal cavity. Meanwhile, enteric-coated nanoparticles were swallowed and dissolved in the GIT. Intuitively, the absorption process was prolonged. The in vitro release characteristics of all the tablets were studied in comparison with a commercial tablet (CT). Additionally, evaluation of the in vivo pharmacokinetic profile of both the prepared and commercial tablets was performed in humans. The dual function tablet disintegrated in 58 s at pH 5.5. In vivo, noncompartmental pharmacokinetic analysis showed concomitant rapid absorption, possibly from the coat, followed by prolonged absorption from the core. Successfully, these good results confirm that combined rapid and prolonged MCZ therapy with the prepared dual function orodissolvable/dispersible tablet could be a promising oral drug delivery system to enhance convenience for patients. Hopefully, dual function tablets will confer a benefit through the accommodation of more than a single medication in the case of multiple therapies.

Full-factor design of experiment application in the development of printing ink for binder jetting 3D printed preparation / 药学学报

The development of printing ink is a challenge for binder jetting 3D printed preparations, which directly determines the quality of the printed product. This study adopted a 23 full-factor Design of Experiment (DoE) with three central points to optimize the printing ink composition of levetiracetam 3D printed dispersible tablet based on the concept of Quality by Design. Firstly, using polyvinyl pyrrolidone K30, glycerin and polysorbate 20 as independent variables based on 40% (v/v) isopropanol aqueous solution, and weight variation, hardness, friability and dispersion uniformity of the printed tablets were used as dependent variables. Then obtained the design space of the printing ink prescription by DoE model analysis, and the response optimizer was used to obtain the optimal printing ink prescription: isopropanol aqueous solution containing 0.1% (w/w) polyvinyl pyrrolidone K30 and 4.0% (w/w) glycerin. The jetting mechanism and wettability of the printing ink were analyzed, and different strengths of personalized 3D printed tablets were prepared and characterized, which verified the rationality of the printing ink formulation. This study provided a reference for the development of printing ink for binder jetting 3D printed preparations.

[Effect of Tiaoli Piwei needling technique on diabetic gastroparesis and transmembrane protein 16A].

OBJECTIVE: To observe the therapeutic effect of Tiaoli Piwei needling technique (acupuncture for regulating spleen and stomach) on diabetic gastroparesis (DGP), and to explore its possible mechanism. METHODS: A total of 128 patients with DGP were randomized into an observation group (64 cases, 4 cases dropped off) and a control group (64 cases, 4 cases dropped off). On the basis of intervention on controlling blood glucose by western medication, Tiaoli Piwei needling technique was adopted at Zhongwan (CV 12), Zusanli (ST 36), Yinlingquan (SP 9), Xuehai (SP 10), Sanyinjiao (SP 6), Diji (SP 8), etc. in the observation group, once a day. Mosapride citrate dispersible tablet 5 mg was given orally 3 times a day in the control group. The treatment was given 6 times a week in the both groups, and totally 4-week treatment was required. Before and after treatment, the DGP symptom score, serum content of transmembrane protein 16A (ANO1) were observed, and the clinical therapeutic effect and the safety were evaluated in the both groups. RESULTS: After treatment, the each subitem score (belching, abdominal distension, inappetence, nausea and vomiting, epigastric pain, abnormal defecation) and the total score of DGP symptom were decreased in both groups (P<0.05), the subitem scores of belching, abdominal distension, inappetence, nausea and vomiting and the total score in the observation group were lower than those in the control group (P<0.05). After treatment, the serum contents of transmembrane protein 16A were reduced in both groups (P<0.05), and that in the observation group was lower than the control group (P<0.05). The total effective rate was 86.7% (52/60) in the observation group, which was superior to 70.0% (42/60) in the control group (P<0.05). Subcutaneous hematoma occurred in 5 cases in the observation group, which was improved after cold compress without other particular intervention. CONCLUSION: The therapeutic effect of Tiaoli Piwei needling technique on improving symptoms in patients with diabetic gastroparesis is superior to mosapride citrate dispersible tablet, its mechanism may be related to alleviating the damage of interstitial cells of Cajal (ICC).

Preoperative oral zinc tablet decreases incidence of postoperative sore throat.

BACKGROUND AND AIMS: Postoperative sore throat (POST) is very frequently reported after endotracheal intubation. Zinc lozenge has been shown to reduce POST. The aim of this study was to evaluate the effect of dispersible zinc tablet on POST. METHODS: Eighty-eight patients undergoing surgery with endotracheal intubation were randomly allocated into two groups, to either receive dispersible zinc tablet 40 mg (zinc group) or placebo tablet (control group), 30 min preoperatively. Assessment for incidence and severity was performed for POST, on a 4-point scale (0-3) at 0, 30 min, 2, 4, and 24 h postoperatively. The primary outcome was incidence of POST at 4 h postoperatively. Secondary outcome was severity of POST at the 5 evaluation time points postoperatively. Mann-Whitney U test, Fisher's exact, and Chi-square test were used as applicable. RESULTS: At 4 h, there was a significantly lower incidence of POST in zinc group (6.8%) than the control group (31.8%) with a P value of 0.003. Three patients in placebo group complained of severe POST compared to none in the zinc group. The severity of POST was significantly lower in Zinc group than Placebo group at 0 min (P = 0.003), 30 min (P = 0.002), 2 h (P < 0.001), and 4 h (P = 0.001). CONCLUSION: Preoperative administration of 40 mg dispersible zinc tablet effectively reduces the incidence and severity of POST in the immediate postoperative period.

Design and optimization of a child-friendly dispersible tablet containing isoniazid, pyrazinamide, and rifampicin for treating tuberculosis in pediatrics.

Objective: Develop a child-friendly Fixed Dose Combination (FDC) water-dispersible tablet for Tuberculosis (TB) treatment, with 50, 150, and 75 mg of isoniazid, pyrazinamide and rifampicin respectively. This new formulation must contain the lowest number of excipients accepted for pediatrics and fulfill all the pharmacopeia requirements.Significance: At present, there is no adequate market dosage form available for children. There is, however, one in a prequalification phase by the World Health Organization but its composition contains excipients which may not be suitable for pediatrics. Therefore, this new formulation would cover this therapeutic gap.Methods: A factorial design, based on three quantitative factors (compression force and concentration of AcDiSol® and Explosol®) at three levels each, was performed to elucidate their influence over disintegration time and friability. In addition, the influence of the press speed on disintegration time, friability, tensile strength, fineness of dispersion and content uniformity over the target tablet was tested. A stability test was done following ICH guideline for accelerated conditions.Results: Tablets developed with 9% w/w of Explosol® and a compression force of 16 kN disintegrated in less than 3 min and showed a friability below 1% when 15-mm punches were used. The tableting process could be done up to 25 and 50 cycles/minute ensuring good quality attributes when 15 and 12-mm punches were used, respectively. All APIs remained inside the limit of ± 5% of drug content till 6 months of storage.Conclusion: A high-quality child-friendly FDC water-dispersible tablet was developed improving the treatment of TB in pediatric.

Effect of needling technique on diabetic gastroparesis and transmembrane protein 16A / 中国针灸

OBJECTIVE@#To observe the therapeutic effect of needling technique (acupuncture for regulating spleen and stomach) on diabetic gastroparesis (DGP), and to explore its possible mechanism.@*METHODS@#A total of 128 patients with DGP were randomized into an observation group (64 cases, 4 cases dropped off) and a control group (64 cases, 4 cases dropped off). On the basis of intervention on controlling blood glucose by western medication, needling technique was adopted at Zhongwan (CV 12), Zusanli (ST 36), Yinlingquan (SP 9), Xuehai (SP 10), Sanyinjiao (SP 6), Diji (SP 8), etc. in the observation group, once a day. Mosapride citrate dispersible tablet 5 mg was given orally 3 times a day in the control group. The treatment was given 6 times a week in the both groups, and totally 4-week treatment was required. Before and after treatment, the DGP symptom score, serum content of transmembrane protein 16A (ANO1) were observed, and the clinical therapeutic effect and the safety were evaluated in the both groups.@*RESULTS@#After treatment, the each subitem score (belching, abdominal distension, inappetence, nausea and vomiting, epigastric pain, abnormal defecation) and the total score of DGP symptom were decreased in both groups (<0.05), the subitem scores of belching, abdominal distension, inappetence, nausea and vomiting and the total score in the observation group were lower than those in the control group (<0.05). After treatment, the serum contents of transmembrane protein 16A were reduced in both groups (<0.05), and that in the observation group was lower than the control group (<0.05). The total effective rate was 86.7% (52/60) in the observation group, which was superior to 70.0% (42/60) in the control group (<0.05). Subcutaneous hematoma occurred in 5 cases in the observation group, which was improved after cold compress without other particular intervention.@*CONCLUSION@#The therapeutic effect of needling technique on improving symptoms in patients with diabetic gastroparesis is superior to mosapride citrate dispersible tablet, its mechanism may be related to alleviating the damage of interstitial cells of Cajal (ICC).

Evaluating the use of job aids and user instructions to improve adherence for the treatment of childhood pneumonia using amoxicillin dispersible tablets in a low-income setting: a mixed-method study.

OBJECTIVES: We conducted a study to evaluate the use of job aids and simple user instructions to improve adherence for the treatment of childhood pneumonia with amoxicillin dispersible tablet (DT). DESIGN: A mixed-method study implemented in three phases between October 2015 and February 2016. SETTINGS: The study was implemented in two subdistricts of Bangladesh. PARTICIPANTS: Caregivers of children aged 2-59 months, health service providers and key stakeholders at national and district level. INTERVENTIONS: An intervention including training and job aids and user-friendly instructions was introduced in one subdistrict while standard amoxicillin DT packaging and instructions with no training served as the control in the comparison subdistrict. PRIMARY OUTCOME: Adherence behaviour of caregivers of children aged 2-59 months for the treatment of childhood pneumonia with amoxicillin DT. METHODS: We conducted a survey with 56 caregivers in the intervention subdistrict and 38 caregivers in the comparison subdistrict. We also conducted 44 in-depth interviews to evaluate the job aids and user-friendly instructions with healthcare providers and caregivers to assess the feasibility, usability and acceptability of the tools in intervention subdistrict. RESULTS: For 5-day treatment course, 32.1% (95% CI 23.1% to 41.1%) of caregivers in the intervention subdistrict and 2.6% (95% CI 0.3% to 7.8%) in the comparison subdistrict maintained full adherence to the amoxicillin DT treatment for pneumonia. More children under 12 months were given age-appropriate treatment than older children. Key stakeholders and healthcare providers considered the use and integration of the tools into the health system to be feasible and acceptable. CONCLUSIONS: The provision of tools for the treatment of childhood pneumonia with amoxicillin DT had a positive influence on adherence behaviours. These tools can help close information gaps and overcome the barriers posed by medical illiteracy and remembering instructions from providers.

[Study on puerarin dispersible tablet based on solubilization effect of glycyrrhizic acid].

Based on the fact that glycyrrhizic acid can form micelles in aqueous solution and play a role in solubilization, the optimal compatibility ratio between puerarin and glycyrrhizic acid was screened to prepare puerarin-glycyrrhizic acid dispersible tablets and investigate the dissolution of puerarin. The particle size, Zate potential and puerarin dissolution were compared among the micellar solutions with mass ratio of 7∶1, 6∶1, 5∶1, 4∶1, 3∶1 and 2∶1(puerarin to glycyrrhizic acid), and it was found that when the mass ratio of puerarin and glycyrrhizic acid was 5∶1, the micelle showed smallest particle size, uniform distribution, and largest puerarin dissolution, so mass ratio of 5∶1 was determined as the optimal condition. The formulation of puerarin-glycyrrhizic acid dispersible tablets was optimized by single factor and orthogonal test: puerarin 100.0 mg, glycyrrhizin 20.0 mg, polyvinylpolypyrrolidone 24.0 mg as disintegrating agent, microcrystalline cellulose 135.0 mg as stuffing bulking agent, hydroxypropyl methyl cellulose 18.0 mg as adhesive agent, magnesium stearate 2.7 mg as lubricant, and tablet weight of 300.0 mg. High-performance liquid chromatography(HPLC) method was used to determine the content of puerarin in dispersible tablets. Puerarin showed a good linear relationship(r=0.999 8) in the range of 15.5-248 g·L~(-1), with high precision(RSD<2.0%) and good repeatability(RSD<2.0%), and the recovery rate was 101.1%, RSD 0.89%. There was no significant difference in the quantity of puerarin in different batches of puerarin-glycyrrhizic acid dispersible tablets. When the artificial gastric juice was used as the dissolution medium, the dissolution of puerarin in puerarin-glycyrrhizic acid dispersible tablets could reach over 85% within 15 min. When phosphate buffer(pH 6.8) was used as the dissolution medium, the dissolution of puerarin in the puerarin-glycyrrhizic acid dispersible tablets had a faster dissolution rate in vitro, 99.8% in 30 min. Therefore, puerarin-glycyrrhizic acid dispersible tablets could improve the dissolution of puerarin in vitro due to the solubilization effect of glycyrrhizic acid.

Revisiting dispersible milk-drug tablets as a solid lipid formulation in the context of digestion.

Oral delivery of dispersible tablets is a preferred route of administration for paediatrics due to ease of administration and dose control. Milk has gained interest as a drug delivery system due to its ability to dissolve poorly water-soluble drugs. There are no reports of milk tablet formulations being assessed in the context of lipid digestion, which is critical in influencing orally administered drug solubility and bioavailability. Milk-drug tablets were formulated by blending freeze-dried bovine milk or infant formula with the poorly water-soluble drug cinnarizine, which were directly compressed. Tablet strength, friability and dispersibility were quantified and synchrotron X-ray scattering was used to determine the lipid liquid crystalline phases formed during in vitro digestion of dispersed tablets and their effects on drug solubilisation. Tableting had a significant impact on the self-assembly of lipids in redispersed milk tablets whereas no effect was seen for infant formula tablets. Incorporation of the disintegrant poly(vinylpolypyrrolidone) to reduce tablet dispersion times promoted the formation of hexagonal liquid crystalline phases upon digestion but had minimal effect on drug solubilisation. These findings show that similar to the use of liquid milk, the formulation of milk-drug tablets can be used to improve solubilisation of poorly water-soluble drugs.

Study on puerarin dispersible tablet based on solubilization effect of glycyrrhizic acid / 中国中药杂志

Based on the fact that glycyrrhizic acid can form micelles in aqueous solution and play a role in solubilization, the optimal compatibility ratio between puerarin and glycyrrhizic acid was screened to prepare puerarin-glycyrrhizic acid dispersible tablets and investigate the dissolution of puerarin. The particle size, Zate potential and puerarin dissolution were compared among the micellar solutions with mass ratio of 7∶1, 6∶1, 5∶1, 4∶1, 3∶1 and 2∶1(puerarin to glycyrrhizic acid), and it was found that when the mass ratio of puerarin and glycyrrhizic acid was 5∶1, the micelle showed smallest particle size, uniform distribution, and largest puerarin dissolution, so mass ratio of 5∶1 was determined as the optimal condition. The formulation of puerarin-glycyrrhizic acid dispersible tablets was optimized by single factor and orthogonal test: puerarin 100.0 mg, glycyrrhizin 20.0 mg, polyvinylpolypyrrolidone 24.0 mg as disintegrating agent, microcrystalline cellulose 135.0 mg as stuffing bulking agent, hydroxypropyl methyl cellulose 18.0 mg as adhesive agent, magnesium stearate 2.7 mg as lubricant, and tablet weight of 300.0 mg. High-performance liquid chromatography(HPLC) method was used to determine the content of puerarin in dispersible tablets. Puerarin showed a good linear relationship(r=0.999 8) in the range of 15.5-248 g·L~(-1), with high precision(RSD<2.0%) and good repeatability(RSD<2.0%), and the recovery rate was 101.1%, RSD 0.89%. There was no significant difference in the quantity of puerarin in different batches of puerarin-glycyrrhizic acid dispersible tablets. When the artificial gastric juice was used as the dissolution medium, the dissolution of puerarin in puerarin-glycyrrhizic acid dispersible tablets could reach over 85% within 15 min. When phosphate buffer(pH 6.8) was used as the dissolution medium, the dissolution of puerarin in the puerarin-glycyrrhizic acid dispersible tablets had a faster dissolution rate in vitro, 99.8% in 30 min. Therefore, puerarin-glycyrrhizic acid dispersible tablets could improve the dissolution of puerarin in vitro due to the solubilization effect of glycyrrhizic acid.

Pharmacokinetics study of mycophenolic acid in early renal transplant patients / 中国药学杂志

OBJECTIVE: To investigate the pharmacokinetic characteristics of enteric-coated sodium mycophenolate(EC-MPS) or mycophenolate mofetil (MMF) dispersible tablets after multiple oral doses in early renal transplant patients, providing references for the rational use of the study drugs in clinical practice. METHODS: Thirty-eight first-time renal transplant patients were selected and randomly divided into EC-MPS group (n=18) or MMF dispersible tablets group (n=19). The patients received EC-MPS (540 mg, q12h) or MMF dispersible tablets (750 mg, q12h), combined with tacrolimus and methylprednisolone to prevent acute rejection, respectively. Blood samples were collected at pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 h after oral administration on the postoperative day 5. Enzyme multiplied immunoassay technique (EMIT) was employed to determine the plasma concentration of MPA. The main pharmacokinetic parameters of the two durgs were assessed. RESULTS: Pharmacokinetic parameters on the postoperative day 5 of EC-MPS and MMF dispersible tablet were as follows: AUC0-12 h were(43.62±16.20) and(42.02±14.40)mg•h•L-1(P>0.05);ρmax were (17.85±11.32) and (13.96±5.11) mg•L-1(P>0.05);tmax were (2.72±1.74) and(1.32±0.42)h(P0.05); ρ12were(1.84±2.09) and (1.81±1.76) mg•L-1(P>0.05); CL were (14.12±5.30) and (19.66±5.99) L•h-1(P<0.05). Most of the patients revealed a second small peak in the 4-12 h after taking MPA in the two study groups. CONCLUSION: There are large individual differences of pharmacokinetic between EC-MPS and MMF dispersible tablets in early renal transplant patients. It is necessary to carry out therapeutic drug monitoring of MPA to guide the adjustment of drug dosage.

Development and Optimization of Dispersible Tablet of Bacopa monnieri with Improved Functionality for Memory Enhancement.

INTRODUCTION: The Bacopa monnieri is traditional Ayurvedic medicine, and reported for memory-enhancing effects. The Bacoside is poorly soluble, bitter in taste and responsible for the memory enhancement action. Memory enhancer is commonly prescribed for children or elder people. OBJECTIVE: Poor solubility, patient compliance and bitterness were a major driving force to develop taste masked ß-cyclodextrin complex and dispersible tablets. MATERIALS AND METHODS: The inclusion complex of Bacopa monnieri and ß-cyclodextrin was prepared in different molar ratios of Bacopa monnieri by Co-precipitation method. Phase solubility study was conducted to evaluate the effect of ß-cyclodextrin on aqueous solubility of Bacoside A. The characterization was determined by Fourier transformation infrared spectroscopy (FTIR),Differential scanning calorimetry (DSC) and X-ray diffraction study (XRD).Crospovidone and croscarmallose sodium were used as super disintigrant. The 32 full factorial design was adopted to investigate the influence of two superdisintegrants on the wetting time and disntegration time of the tablets. CONCLUSION: The result revels that molar ratio (1:4) of inclusion complex enhance 3-fold solubility. Full factorial design was successfully employed for the optimization of dispersible tablet of B. monnieri. The short-term accelerated stability study confirmed that high stability of B. monnieri in inclusion complex.

Assessment of Efficacy and Safety of Arterolane Maleate-Piperaquine Phosphate Dispersible Tablets in Comparison With Artemether-Lumefantrine Dispersible Tablets in Pediatric Patients With Acute Uncomplicated Plasmodium falciparum Malaria: A Phase 3, Randomized, Multicenter Trial in India and Africa.

BACKGROUND: Administration of artemisinin-based combination therapy (ACT) to infant and young children can be challenging. A formulation with accurate dose and ease of administration will improve adherence and compliance in children. The fixed-dose combination dispersible tablet of arterolane maleate (AM) 37.5 mg and piperaquine phosphate (PQP) 187.5 mg can make dosing convenient in children. METHODS: This multicenter (India and Africa), comparative, parallel-group trial enrolled 859 patients aged 6 months to 12 years with Plasmodium falciparum malaria. Patients were randomized in a ratio of 2:1 to AM-PQP (571 patients) once daily and artemether-lumefantrine (AL) (288 patients) twice daily for 3 days and followed for 42 days. RESULTS: The cure rate (ie, polymerase chain reaction-corrected adequate clinical and parasitological response) in the per-protocol population at day 28 was 100.0% and 98.5% (difference, 1.48% [95% confidence interval {CI}, .04%-2.91%]) in the AM-PQP and AL arms, respectively, and 96.0% and 95.8% (difference, 0.14% [95% CI, -2.68% to 2.95%]) in the intention-to-treat (ITT) population. The cure rate was comparable at day 42 in the ITT population (AM-PQP, 94.4% vs AL, 93.1%). The median parasite clearance time was 24 hours in both the arms. The median fever clearance time was 6 hours in AM-PQP and 12 hours in the AL arm. Both the treatments were found to be safe and well tolerated. Overall, safety profile of both the treatments was similar. CONCLUSIONS: The efficacy and safety of fixed-dose combination of AM and PQP was comparable to AL for the treatment of uncomplicated P. falciparum malaria in pediatric patients. CLINICAL TRIALS REGISTRATION: CTRI/2014/07/004764.

Pharmacokinetic herb-drug interaction of Xuesaitong dispersible tablet and aspirin after oral administration in blood stasis model rats.

BACKGROUND: Xuesaitong dispersible tablet (XST) product has been clinically proven to be effective for treating cardio-cerebrovascular disease. Furthermore, herb-drug interactions between the XST product and drugs that are commonly co-administered, such as aspirin (ASA), must be explored to ensure safe clinical use. STUDY DESIGN AND METHODS: The current study aims to investigate whether the XST product interacts with ASA when they are administered concomitantly to ensure safety and efficacy. A ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the simultaneous determination of ginsenoside Rg1 (Rg1), ginsenoside Rd (Rd), notoginsenoside R1 (R1) and salicylic acid (SA) in rat plasma to investigate the pharmacokinetic interaction of XST and ASA in blood stasis model rats. RESULTS AND CONCLUSION: The ASA and XST combination noticeably altered R1 and Rg1 absorption, distribution and disposition. This study indicates that co-administration of XST and ASA can cause an apparent herb-drug pharmacokinetic interaction in blood stasis model rats.

Relative Bioavailability of a Dolutegravir Dispersible Tablet and the Effects of Low- and High-Mineral-Content Water on the Tablet in Healthy Adults.

Dolutegravir (DTG) is approved in the United States to treat HIV-1-infected patients weighing ≥30 kg. A dispersible DTG tablet formulation was recently developed for pediatric patients. This study compares the pharmacokinetics (PK) of the dispersible tablet with that of a previously evaluated granule formulation. In this randomized, open-label, crossover study, 15 healthy adults received single oral doses of DTG 20 mg every 7 days across 5 treatment arms: granules consumed immediately after mixture with purified water, dispersible DTG consumed immediately after reconstitution in low-mineral-content (LMC) or high-mineral-content (HMC) water, and dispersible DTG consumed 30 minutes after dispersal in LMC or HMC water. Primary endpoints were bioavailability of immediately consumed dispersible tablet in LMC water relative to granule formulation reconstituted in purified water and PK of the dispersible tablet. Secondary endpoints included tolerability and palatability. The DTG dispersible tablet showed equivalent exposures to the granule formulation with geometric least-squares mean treatment ratios of 1.06 and 1.12 for AUC0-∞ and Cmax , respectively. DTG PK parameters were unaffected by mineral content or the 30-minute delay. Adverse events were mild; only nausea (n = 1) was considered drug related. DTG exposure observed with the dispersible tablet supports evaluation of this formulation for further development.

Pharmacokinetics Study of Mycophenolate Mofetil Dispersible Tablets in Early Renal Transplant Patients / 中国药学杂志

OBJECTIVE: To develop an UPLC method for the determination of mycophenolic acid(MPA) for studying the pharmacokinetics of mycophenolate mofetil(MMF) dispersible tablets after multiple oral doses in early kidney transplant recipients for the rational use in the clinical practice. METHODS: A total of 15 Chinese postoperative renal transplant recipients were given a multiple-dose of MMF (750 mg, q12 h) for 6 d. Their blood specimens (2 mL) were collected at 0 and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 h after drug oral administration on day 7. The concentrations of MPA in plasma were determined using UPLC-UV. The main pharmacokinetic parameters were assessed. RESULTS: Determination of MPA had good linearity in the concentration range of 0.1-40 μg·mL-1, lower limit of quantization was 0.10 μg·mL-1.The main pharmacokinetic parameters on day 7 of MMF dispersible tablets were as follows: AUC0-12 h was (24.63±9.51) μg·h·mL-1, ρmax was (6.51±3.27) μg·mL-1, tmax was (1.83±1.30) h, ρ0 was (1.26±0.99) μg·mL-1, CL was (34.66±12.45) L·h-1. Most of the patients revealed a second small peak in the 4-12 h. CONCLUSION: This established method is simple, rapid and suitable for determination of MPA in human plasma.Interindividual variability in AUC0-12 h, ρmax and ρ0 values was considerable in the early renal transplant patients. The MPA exposures under the fixed dose of MMF are low. It is necessary to monitor the MPA-AUC0-12 h to guide the adjustment of drug dosage.